Efficient Semiparametric Inference Under Two-Phase Sampling, With Applications to Genetic Association Studies

<p>In modern epidemiological and clinical studies, the covariates of interest may involve genome sequencing, biomarker assay, or medical imaging and thus are prohibitively expensive to measure on a large number of subjects. A cost-effective solution is the two-phase design, under which the outcome and inexpensive covariates are observed for all subjects during the first phase and that information is used to select subjects for measurements of expensive covariates during the second phase. For example, subjects with extreme values of quantitative traits were selected for whole-exome sequencing in the National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP). Herein, we consider general two-phase designs, where the outcome can be continuous or discrete, and inexpensive covariates can be continuous and correlated with expensive covariates. We propose a semiparametric approach to regression analysis by approximating the conditional density functions of expensive covariates given inexpensive covariates with B-spline sieves. We devise a computationally efficient and numerically stable EM-algorithm to maximize the sieve likelihood. In addition, we establish the consistency, asymptotic normality, and asymptotic efficiency of the estimators. Furthermore, we demonstrate the superiority of the proposed methods over existing ones through extensive simulation studies. Finally, we present applications to the aforementioned NHLBI ESP. Supplementary materials for this article are available online</p

Effects of Alkyl Chain Length and Substituent Pattern of Fullerene Bis-Adducts on Film Structures and Photovoltaic Properties of Bulk Heterojunction Solar Cells

A series of alkoxycarbonyl-substituted dihydronaphthyl-based [60]­fullerene bis-adduct derivatives (denoted as C2BA, C4BA, and C6BA with the alkyl chain of ethyl, <i>n</i>-butyl, and <i>n</i>-hexyl, respectively) have been synthesized to investigate the effects of alkyl chain length and substituent pattern of fullerene bis-adducts on the film structures and photovoltaic properties of bulk heterojunction polymer solar cells. The shorter alkyl chain length caused lower solubility of the fullerene bis-adducts (C6BA > C4BA > C2BA), thereby resulting in the increased separation difficulty of respective bis-adduct isomers. The device performance based on poly­(3-hexylthiophene) (P3HT) and the fullerene bis-adduct regioisomer mixtures was enhanced by shortening the alkyl chain length. When using the regioisomerically separated fullerene bis-adducts, the devices based on <i>trans</i>-2 and a mixture of <i>trans</i>-4 and <i>e</i> of C4BA exhibited the highest power conversion efficiencies of ca. 2.4%, which are considerably higher than those of the C6BA counterparts (ca. 1.4%) and the C4BA regioisomer mixture (1.10%). The film morphologies as well as electron mobilities of the P3HT:bis-adduct blend films were found to affect the photovoltaic properties considerably. These results reveal that the alkyl chain length and substituent pattern of fullerene bis-adducts significantly influence the photovoltaic properties as well as the film structures of bulk heterojunction solar cells

Mean reaction times to negative and positive words after conscious viewing of self- and other-faces.

<p>Mean reaction times to negative and positive words after conscious viewing of self- and other-faces.</p

Schematic representation of the experimental paradigm for the main session in Experiment 1.

<p>In Experiment 2, the noise patches were replaced by the same face picture presented to the other eye.</p

Mean reaction times to valenced words by face primes at different self-esteem levels.

<p>For this and the following figures, † <i>p</i><.08, * <i>p</i><.05, ** <i>p</i><.01, *** <i>p</i><.001, errors bars indicate standard error.</p

XBJ significantly ameliorated inflammation in mouse livers that have undergone IRI.

<p>B6 mice were either sham operated (sham group) or subjected to 90 minutes of partial warm ischemia, followed by 6 hours of reperfusion. XBJ (2 ml/kg iv) was given either before ischemia (before group) or after initiation of reperfusion (after group), while the same volume of normal saline was administered in the vehicle group. Serum and liver samples were harvested (n = 3-6/group). (A) qRT-PCR detection of CXCL-1, CXCL-10, IL-1β, IL-6 and TNF-a. Data were normalized to HPRT gene expression and expressed as fold increase above the sham group (set as 1). (B) ELISA detection of MCP-1, IL-6 and TNF-α. Accumulation of neutrophils and macrophages after administration of XBJ was analyzed by (C) Ly-6G (neutrophils), (D) CD68 (macrophages) immunohistochemical staining (Original magnifications, 200×magnification) and (E) MPO levels in IRI liver lobes. (F) ROS was detected using the fluorescent probe DCFH-DA. Data were expressed as mean±SEM. *P<0.05, **P<0.01,*** P <0.001.</p

XBJ suppressed inflammasome activation in mouse livers that have undergone IRI.

<p>B6 mice were either sham operated (sham group) or subjected to 90 minutes of partial warm ischemia, followed by 6 hours of reperfusion. XBJ (2 ml/kg iv) was given either before ischemia (before group) or after initiation of reperfusion (after group), while the same volume of normal saline was administered in the vehicle group. Liver samples were then harvested (n = 3-6/group). (A) Western blot analysis of NLRP3, ASC, Caspase-1 and IL-1β in IRI liver lobes. Representative blots from at least three mice were shown. *, non-specific bands. (B) Densitometric analyses of western blot for NLRP3, ASC, Caspase-1 and IL-1β. Values shown were relative to sham group (set as 1). Compared to sham group, *p<0.05; **p<0.01; ***p<0.001. NS, no significance.</p

Multi-target anti-inflammatory effect of XBJ Injection.

<p>The inflammation associated network was constructed using network pharmacology technology, in which XBJ showed anti-inflammatory effect through a multi-target mode of action. This network consisted of nodes and edges, and inflammation associated nodes were linked through edges, while red nodes stand for targets of XBJ with experimental investigations at different levels (<i>i</i>.<i>e</i>. BCL2, CASP1, TNF, IL1B, CCL2, PYCARD, NLRP3, CXCL1, CXCL10, IL6). Size of node was in proportion to the numbers of links to the node, that is the bigger size node had more associated genes. Inflammation associated genes were obtained from HuGE Navigator (version 2.0)</p

Synthesis and Isolation of <i>cis</i>-2 Regiospecific Ethylene-Tethered Indene Dimer–[70]Fullerene Adduct for Polymer Solar Cell Applications

Although the utilization of [70]­fullerene bis-adducts can enhance the power conversion efficiencies of polymer solar cells (PSCs) owing to their strong absorption intensities and high-lying lowest unoccupied molecular orbital energy levels, this synthetic strategy typically yields a mixture of regioisomers that would mask the intrinsic device performances depending on the substituent pattern on the [70]­fullerene derivatives. In this study, a single <i>cis</i>-2 regioisomer of C₇₀ bis-adduct (<i>cis</i>-2-[70]­BIEC) has been prepared for the first time by the same strategy that had been applied to [60]­fullerene to obtain a regioisomerically pure C₆₀ bis-adduct (<i>cis</i>-2-[60]­BIEC). Diels–Alder reaction was conducted between a rationally designed ethylene-tethered indene dimer and [70]­fullerene, followed by isolation using high-performance liquid chromatography suitable for the separation of fullerene derivatives. A series of structural analysis techniques including NMR spectroscopies and X-ray crystallography were used to identify the absolute configuration of the bis-adduct. A systematic study on the optical, electrochemical, and photovoltaic properties of <i>cis</i>-2-[70]­BIEC as well as the corresponding regioisomer mixture (bis-[70]­BIEC) and the monoadduct (α-mono-[70]­BIEC) has been performed to examine the effect of the pure <i>cis</i>-2 regioisomer. More importantly, their properties are compared with those of <i>cis</i>-2-[60]­BIEC to address the effect of fullerene cage structures, that is, C₆₀ versus C₇₀. The PSC based on <i>cis</i>-2-[70]­BIEC and poly­(3-hexylthiophene) showed a remarkable power conversion efficiency of 4.2%, which is higher than those with bis-[70]­BIEC (2.2%), α-mono-[70]­BIEC (2.2%), <i>cis</i>-2-[60]­BIEC (2.8%), and even a prevalent high-performance C₇₀ monoadduct ([70]­PCBM, 3.8%). Our synthetic strategy will pave the way for further development on the rational design and isolation of single fullerene bis-adduct regioisomers exhibiting high device performances

Sequence of primer pairs used in real-time quantitative PCR.

<p>Sequence of primer pairs used in real-time quantitative PCR.</p